Risk factors associated with chronic kidney disease of unknown origin (Ckdu) in North Central Province (NCP) of Sri Lanka: An analysis of evidence to date

© 2020 The Authors. Published by [Name of Publisher]. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://acquaintpublications.org/journals/journal-of-medical-case-reports-and-case-series/current-issue/12Chronic kidney disease of unknown origin (CKDu) is a global burden among the agricultural communities, this is a non-communicable disease (NCD) which is asymptomatic and irreversible until latter stages of the disease. The disease has no common features unlike chronic kidney diseases (CKD’s) making early detection impossible in the patients. The most recent form of CKDu was reported in India, known as the Indian CKDu in late 2010’s. In Sri Lanka, CKDu is highly prevalent in the north central province of the country with nearly15.1%-22.9% presented with the disease. This region is a dry-zone in which agricultural and farming activities are carried out as the main occupation. Several studies have been carried out linking CKDu to various factors such as heavy metals in water, agrochemicals, heat, dehydration and socio-demographics in NCP. Despite several researches being conducted none of them were able to prove the root cause and causative factors of the disease. Using the available articles online, studies from countries such as India, Nicaragua, Sri Lanka and South America were chosen in which heat stress, dehydration, heavy metal involvement, agrochemicals were common causative factors reported in these geographical locations. Several studies analyzed indicate that the affected CKDu population were part of the agricultural community in rural areas with less or no proper high school education and family history with CKDu. Recent findings do suggest that a combination study involving socio-demographical data and geographical data will help to end the CKDu debate worldwide and provide new insights into early diagnosis

Chronic Kidney Disease of Unknown aetiology (CKDu) and multiple-ion interactions in drinking water

Recent experimental work on the nephrotoxicity of contaminants in drinking water using laboratory mice, motivated by the need to understand the origin of chronic kidney disease of unknown aetiology is examined within our understanding of the hydration of ions and proteins. Qualitative considerations based on Hofmeister-type action of these ions, as well as quantitative electrochemical models for the Gibbs free-energy change for ion-pair formation are used to explain why Cd$^{2+}$ in the presence of F$^-$ and water hardness due to Mg$^{2+}$ ions (but not Ca$^{2+}$) can be expected to be more nephrotoxic, while AsO$_3^{3-}$ in the presence of F$^-$ and hardness may be expected to be less nephrotoxic. The analysis is applied to a variety of ionic species typically found in water to predict their likely combined electro-chemical action. These results clarify the origins of chronic kidney disease in the north-central province of Sri Lanka. The conclusion is further strengthened by a study of the dietary load of Cd and As, where the dietary loads are found to be safe, especially when the mitigating effects of micronutrient ionic forms of Zn and Se, as well as corrections for bio-availability are taken in to account. The resulting aetiological picture supports the views that F$^-$, Cd$^{2+}$ (to a lesser extent), and Mg$^{2+}$ ions found in stagnant household well water act together with enhanced toxicity, becoming the most likely causative factor of the disease. Similar incidence of CKDu found in other tropical climates may have similar geological origins.Comment: 14 pages, one figur

Is the staple diet eaten in Medawachchiya, Sri Lanka, a predisposing factor in the development of chronic kidney disease of unknown etiology? - A comparison based on urinary β2-microglobulin measurements

BACKGROUND: Exact mechanism of causation of chronic kidney disease of unknown etiology (CKDu) in Sri Lanka is not described to date, despite the identification of possible multiple risk factors. Questions have been raised as to why only some are affected while others remain intact, though they are inhabitants of the same locality. METHODS: Comparative studies were carried out, assessing urinary β(2) microglobulin (β(2)m) and the dietary patterns of CKDu patients and age sex matched non-CKDu subjects. Urinary β2m levels of spot urine samples were analyzed using the Enzyme-linked Immunosorbent assay (ELISA) and dietary patterns were studied using twenty four hour dietary recalls and frequency consumption of foods of animal origin performed on three occasions at six months intervals within a period of one and half years. RESULTS: The mean urinary β(2)m level of CKDu patients from Medawachchiya was significantly (p < 0.05) higher when compared with that of the non-CKDu subjects. The mean urinary β(2)m level of the non-CKDu subjects was within the reference limits for spot urine samples (0 – 0.3 μg/mL). White raw rice was the staple diet of both CKDu patients and non-CKDu subjects and the level of consumption was almost the same. The consumption of fresh water fish products of CKDu patients under high (14, 14%), moderate (36, 36%), low (26, 26%) and less (20, 20%) categories did not show significant variations (p > 0.05) compared to non-CKDu subjects. CONCLUSIONS: Staple food in diet and the consumption pattern of CKDu patients from Medawachchiya were similar to that of non-CKDu subjects from the same area despite their urinary β(2)m concentration being significantly higher

Prevalence and risk factors for chronic kidney disease of unknown cause in Malawi: a cross-sectional analysis in a rural and urban population

Background: An epidemic of chronic kidney disease of unknown cause (CKDu) is occurring in rural communities in tropical regions of low-and middle-income countries in South America and India. Little information is available from Southern African countries which have similar climatic and occupational characteristics to CKDu-endemic countries. We investigated whether CKDu is prevalent in Malawi and identified its potential risk factors in this setting. / Methods: We conducted a cross-sectional study from January–August 2018 collecting bio samples and anthropometric data in two Malawian populations. The sample comprised adults > 18 years (n = 821) without diabetes, hypertension, and proteinuria. Estimates of glomerular filtration rate (eGFR) were calculated using the CKD-EPI equation. Linear and logistic regression models were applied with potential risk factors, to estimate risk of reduced eGFR. / Results: The mean eGFR was 117.1 ± 16.0 ml/min per 1.73m2 and the mean participant age was 33.5 ± 12.7 years. The prevalence of eGFR< 60 was 0.2% (95% confidence interval (95% CI) 0.1, 0.9); the prevalence of eGFR< 90 was 5% (95% CI =3.2, 6.3). We observed a higher prevalence in the rural population (5% (3.6, 7.8)), versus urban (3% (1.4, 6.7)). Age and BMI were associated with reduced eGFR< 90 [Odds ratio (OR) (95%CI) =3.59 (2.58, 5.21) per ten-year increment]; [OR (95%CI) =2.01 (1.27, 3.43) per 5 kg/m2 increment] respectively. No increased risk of eGFR < 90 was observed for rural participants [OR (95%CI) =1.75 (0.50, 6.30)]. / Conclusions: Reduced kidney function consistent with the definition of CKDu is not common in the areas of Malawi sampled, compared to that observed in other tropical or sub-tropical countries in Central America and South Asia. Reduced eGFR< 90 was related to age, BMI, and was more common in rural areas. These findings are important as they contradict some current hypothesis that CKDu is endemic across tropical and sub-tropical countries. This study has enabled standardized comparisons of impaired kidney function between and within tropical/subtropical regions of the world and will help form the basis for further etiological research, surveillance strategies, and the implementation and evaluation of interventions

Nephrotoxic Contaminants in Drinking Water and Urine, and Chronic Kidney Disease in Rural Sri Lanka

Chronic kidney disease of unknown (“u”) cause (CKDu) is a growing public health concern in Sri Lanka. Prior research has hypothesized a link with drinking water quality, but rigorous studies are lacking. This study assesses the relationship between nephrotoxic elements (namely arsenic (As), cadmium (Cd), lead (Pb), and uranium (U)) in drinking water, and urine samples collected from individuals with and/or without CKDu in endemic areas, and from individuals without CKDu in nonendemic areas. All water samples—from a variety of source types (i.e., shallow and deep wells, springs, piped, and surface water)—contained extremely low concentrations of nephrotoxic elements, and all were well below drinking water guideline values. Concentrations in individual urine samples were higher than, and uncorrelated with, those measured in drinking water, suggesting potential exposure from other sources. Mean urinary concentrations of these elements for individuals with clinically diagnosed CKDu were consistently lower than individuals without CKDu both in endemic and nonendemic areas. This likely stems from the inability of the kidney to excrete these toxic elements via urine in CKDu patients. Urinary concentrations of individuals were also found to be within the range of reference values measured in urine of healthy unexposed individuals from international biomonitoring studies, though these reference levels may not be safe for the Sri Lankan population. The results suggest that CKDu cannot be clearly linked with the presence of these contaminants in drinking water. There remains a need to investigate potential interactions of low doses of these elements (particularly Cd and As) with other risk factors that appear linked to CKDu prior to developing public health strategies to address this illness

IDENTIFYING RISK FACTORS FOR CHRONIC KIDNEY DISEASE OF UNKNOWN ORIGIN IN SIX CENTRAL AMERICAN COUNTRIES AND HOUSTON, TEXAS

Chronic kidney disease (CKD) is a public health problem that is recognized worldwide. The type of CKD in Central America does not fit the “usual” CKD encountered in countries with upper middle-income economies, and is also often referred to as CKD of undetermined cause (CKDu). Evidence suggests that CKDu is a disease of occupational origin that can be brought on by a combination of exposures: hot environments, high physical job demands, inadequate hydration protocols, and effects of other nephrotoxic agents. Many gaps remain in knowledge related to CKDu and its putative risk factors, geographic distribution, distributions of renal function in certain demographics and countries as well as regarding feasibility of data collection and analytic methods. To address some of these gaps, I 1) estimated the prevalence and geographic distribution of potential CKDu risk factors among industry sectors in the six Spanish-speaking countries of Central America; 2) mapped the geographic variations of temperature patterns in relation to suspected CKDu risk factors and work-related CKD in the same countries; and 3) field tested the Disadvantaged Populations estimated Glomerular Filtration Rate (eGFR) Epidemiology (DEGREE) study protocol, outdoor point-of-care (POC) testing for serum creatinine, and a new risk factor module on CKDu for future use in U.S. outdoor Hispanic workers. A national representative survey titled The Second Central American Survey of Working Conditions and Health (II ECCTS by its Spanish acronym) was administered to a minimum of 1,500 workers per country, of both sexes, formal and informal workers, and in both urban and rural settings. The data from the II ECCTS were used to estimate the prevalence of CKDu risk factors and CKD risk. Overall descriptive statistics, prevalence of possible CKD and work-related CKD, and prevalence of CKDu risk factors and their distribution were calculated for the overall Central American region, and stratified by economic sector. Secondly, data collected from the II ECCTS were also used to better characterize the climate patterns and the geographic distribution of suspected CKDu risk factors in order to create a weather map to identify possible new “hot spots” in Central America. Finally, we conducted a pilot study of 50 Hispanic outdoor workers in Houston, where they completed the DEGREE and CKDu questionnaires, had anthropometrics and paired blood samples obtained for POC and laboratory assays of renal function at two different points in time (fall and spring). Findings from the national representative survey II ECCTS supplement the prior literature, demonstrating a high prevalence of self-attributed work-related CKD among 30 to 49-year-old mestizo males who worked in the primary and secondary sectors, and had physically demanding jobs. Geographically, most work-related CKD was concentrated in the central to western region of Central America associated with warm temperatures and also overlapped with persons reporting two or more CKDu risk factors. Moreover, there were several geographic areas of CKDu risk factors with no reported work-related CKDu, possibly reflecting as yet-undiscovered clusters of the disease. Implementation of the DEGREE and the new CKDu module was straightforward and well understood. The POC device performed well in the field, with some adjustment in methods when temperature readings were out of range. A combination of these methods can allow researchers to further explore CKDu and its risk factors both in new parts of Central America as well as in the U.S. among similar worker populations. This knowledge is needed so that preventive measures and interventions can be designed and implemented to prevent future cases of CKDu

Possible link of Chronic arsenic toxicity with Chronic Kidney Disease of unknown etiology in Sri Lanka

In recent years a significant increase in number of patients of Chronic Kidney Disease of unknown etiology (CKDu) has been observed in some parts of Sri Lanka, especially in the North Central Province. A case control study has been performed with the intention of determining the prevalence of clinical features of Chronic Arsenic Toxicity (CAT) among CKDu patients in Padavi Sripura divisional secretarial area in Trincomalee District, Sri Lanka. Clinical assessment were done in diagnosed CKDu patients (n=125) and non-CKDu persons (n=180) as the control group. Hair and urine samples collected from both CKDu patients and controls were analyzed for presence of arsenic using Atomic Absorption Spectrometry equipped with Hydride generator (HG-AAS).The results revealed that 68% of CKDu patients and 28% of the controls had urine arsenic levels above 21 µg/g creatinine, which is considered the point of threshold for manifestation of early renal changes that can be developed in to chronic kidney disease. Among the CKDu patients, 48% and 17.4% of the subjects in the control group have fulfilled the criteria to be diagnosed CAT, indicating the potential link between CAT and CKDu. Agrochemicals could be the possible source for this contamination of arsenic since no reported work is available to indicate the presence of arsenic in the bedrocks of Sri Lanka.   Key words: Chronic kidney disease, arsenic, agrochemicals, Sri Lank